The overall goal of this proposal is to examine the utility of immunohistochemistry in identifying intramammary lymphatic invasion (ILI) and blood vessel invasion (IBI) by breast carcinomas, and to evaluate the prognostic significance of these findings. Recent studies have indicated that the presence of ILI and IBI has prognostic importance and may be a useful indicator in guiding adjuvant therapy. However, vascular and lymphatic channels may be difficult to recognize because of tissue shrinkage artifacts, fibrosis and inflammation; furthermore, there may be inter-observer variation in interpreting ILI and IBI. Our approach involves the use of immunohistochemical techniques to permit the objective demonstration of ILI and IBI by breast carcinoma. The independent evaluation of immunohistochemical preparations by investigators at 3 different institutions will address the issue of inter-observer variation. We propose to evaluate the utility of immunohistochemistry in the identification of lymphatic and blood vessels, and to analyze retrospectively a series of breast carcinomas for the presence of ILI and IBI. The immunohistochemical demonstration of the endothelial cell markers Factor VIII Related Antigen and ABH blood group isoantigens and of the basement membrane component laminin will delineate lymphatic and blood vessels in routinely processed tissue, permitting the use of objective criteria in the identification of tumor emboli. The presence of ILI and IBI can then be correlated with survival patterns of patients, standard morphologic prognostic parameters and with known epidemiologic risk factors. These studies will have the potential of determining if ILI and IBI are useful in identifying patients who are at risk of developing subsequent local recurrence or distant metastases; such patients may benefit from postoperative adjuvant chemo- and radiotherapy regimens.